Modified coptisine derivatives as an inhibitor against pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg virus by molecular docking and molecular dynamics simulation-based drug design approach.

During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses.

CRISPR­based diagnostic approaches: Implications for rapid management of future pandemics (Review).

Sudden viral outbreaks have increased in the early part of the 21st century, such as those of severe acute respiratory syndrome coronavirus (SARS­CoV), Middle East respiratory syndrome corona virus, and SARS­CoV­2, owing to increased human access to wildlife habitats. Therefore, the likelihood of zoonotic transmission of human­associated viruses has increased. The emergence of severe acute respiratory syndrome coronavirus 2 in China and its spread worldwide within months have highlighted the need to be ready with advanced diagnostic and antiviral approaches to treat newly emerging diseases with minimal harm to human health. The gold­standard molecular diagnostic approaches currently used are time­consuming, require trained personnel and sophisticated equipment, and therefore cannot be used as point­of­care devices for widespread monitoring and surveillance. Clustered regularly interspaced short palindromic repeats (CRISPR)­associated (Cas) systems are widespread and have been reported in bacteria, archaea and bacteriophages. CRISPR­Cas systems are organized into CRISPR arrays and adjacent Cas proteins. The detection and in­depth biochemical characterization of class 2 type V and VI CRISPR­Cas systems and orthologous proteins such as Cas12 and Cas13 have led to the development of CRISPR­based diagnostic approaches, which have been used to detect viral diseases and distinguish between serotypes and subtypes. CRISPR­based diagnostic approaches detect human single nucleotide polymorphisms in samples from patients with cancer and are used as antiviral agents to detect and destroy viruses that contain RNA as a genome. CRISPR­based diagnostic approaches are likely to improve disease detection methods in the 21st century owing to their ease of development, low cost, reduced turnaround time, multiplexing and ease of deployment. The present review discusses the biochemical properties of Cas12 and Cas13 orthologs in viral disease detection and other applications. The present review expands the scope of CRISPR­based diagnostic approaches to detect diseases and fight viruses as antivirals.